Small Size For Gestational Age Research Articles

Paternal Jail Incarceration and Birth Outcomes: Evidence from New York City, 2010-2016.

To examine population-level associations between paternal jail incarceration during pregnancy and infant birth outcomes using objective measures of health and incarceration. We use multivariate logistic regression models and linked records on all births and jail incarcerations in New York City between 2010 and 2016. 0.8% of live births were exposed to paternal incarceration during pregnancy or at the time of birth. After accounting for parental sociodemographic characteristics, maternal health behaviors, and maternal health care access, paternal incarceration during pregnancy remains associated with late preterm birth (OR = 1.34, 95% CI = 1.21, 1.48), low birthweight (OR = 1.39, 95% CI = 1.27, 1.53), small sizefor gestational age (OR = 1.35, 95% CI = 1.17, 1.57), and NICU admission (OR = 1.14, 95% CI = 1.05, 1.24). We found strong positive baseline associations (p < 0.001) between paternal jail incarceration during pregnancy with probabilities of all adverse outcomes examined. These associations did not appear to be driven purely by duration or frequency of paternal incarceration. These associations were partially explained by parental characteristics, maternal health behavior, and health care. These results indicate the need to consider paternal incarceration as a potential stressor and source of trauma for pregnant women and infants.

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons

BackgroundMany pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.MethodsFrom December 14, 2020, to February 28, 2021, we used data from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.ResultsA total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) were pregnancy losses and 712 (86.1%) were live births (mostly among participants vaccinated in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).ConclusionsPreliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Maternal phthalate urine concentrations, fetal growth and adverse birth outcomes. A population-based prospective cohort study

ImportanceExposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth. ObjectiveTo assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure. DesignPopulation-based prospective cohort study, the Generation R Study (2002–2006). Data analysis was performed from November 2019 to June 2020. SettingRotterdam, the Netherlands. Participants1379 pregnant women. ExposuresMaternal phthalate metabolites urine concentrations in first, second and third trimester. Main outcomes and measuresFetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth. ResultsHigher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences −0.08 (95% CI −0.14 to −0.02) SDS and −0.09 (95% CI −0.16 to −0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations. Conclusions and relevanceHigher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.

Improved Survival of Periviable Infants after Alteration of the Threshold of Viability by the Neonatal Resuscitation Program 2015.

Periviable infants (PIs) born at 22–25 weeks gestational age (wGA) have a variable survival rate (49.7–86.2%) among hospitals. One factor involved in this difference may be the definition of the threshold of viability. The American Academy of Pediatrics revised the neonatal resuscitation program in late 2015 (NRP 2015) and altered the threshold of viability from 23 to 22 wGA. The impact on the survival of PIs after the guideline alteration has seldom been discussed. Since 2016, the unit of this study has implemented the renewed guideline for PIs. We retrospectively reviewed and analyzed the survival and clinical variables of PIs before and after implementation of the guideline, which included a 10-year cohort in a single center in Taiwan. There were 168 PIs enrolled between 2010 and 2019 (Epoch-I, 2010–2015; Epoch-II, 2016–2019), after excluding those with congenital anomalies and parent-decided comfort care. Compared to those in Epoch-I, the PIs in Epoch-II had significantly higher odds ratios (2.602) (95% confidence interval: 1.170–5.789; p = 0.019) for survival. Younger gestational age, small size for gestational age, cesarean delivery, low blood pH at birth, and surfactant therapeutic treatment were found to be significant risk factors associated with the survival of PIs (p < 0.05 for each). The altered threshold of viability by NRP 2015 may impact the survival of PIs. However, long-term follow-up for surviving PI is required in the future.

Desfechos em fetos e recém-nascidos expostos a infecções na gravidez.

To analyze outcomes in fetuses and newborns exposed to infections during pregnancy. Cross-sectional, quantitative study, carried out in a public maternity hospital in Maceió, Alagoas, Brazil. The sample consisted of 145 medical records of pregnant women admitted between 2015 and 2018 with possible vertically transmitted infections. Incomplete medical records or those that did not make it possible to describe fetal/neonatal exposure were excluded. The chi-squared test was used to verify the association between variables. A greater occurrence of congenital syphilis was observed (28.8%). There was more than one outcome in the same individual, such as low birth weight (39%), respiratory distress (20.5%), oligohydramnios (20%), congenital malformation and small size for gestational age (10.8%). Maternal infections and the number of prenatal visits revealed an association with fetal/neonatal outcome (p ≤ 0.05). The data obtained indicate the occurrence of unfavorable fetal/neonatal outcomes when related to neonatal infections and indicate the need for strategies that strengthen the coping with vertical transmissions.

Effects of low-molecular-weight heparin and aspirin in recurrent pre-eclampsia: A stratified cohort study.

To evaluate the effects of low-molecular-weight heparin (LMWH) combined with low-dose aspirin (LDA) in pregnant women with a history of pregnancy-related hypertensive disorders. In the current retrospective stratified cohort study, 33 women with previous hypertensive disorders of pregnancy treated with LMWH and LDA were compared with 37 control women who did not undergo LMWH or LDA treatment. Rates of pre-eclampsia recurrence, placental abruption, and other adverse outcomes for the fetuses and pregnant women were compared in the two groups. The pre-eclampsia recurrence rates were 12/33 (36.4%) in the LMWH+LDA group and 28/37 (75.7%) in the control group (P<0.01). In stratified cohort analysis, pregnant women with a history of early-onset pre-eclampsia, a body mass index of at least 24 (calculated as weight in kilograms divided by the square of height in meters), and aged less than 35years benefited from LMWH+LDA treatment. In women with chronic hypertension or a history of placental abruption there was no protective effect. There were no significant differences in other adverse outcomes such as placental abruption and small size for gestational age in fetuses or pregnant women in the two groups. Administration of LMWH+LDA only lowered the risk of pre-eclampsia recurrence in subgroups of pregnant women with a history of pregnancy-associated hypertensive disorders.

Association between maternal cannabis use and birth outcomes: an observational study

BackgroundAs cannabis consumption is increasing globally, including among pregnant women, there is a critical need to understand the effects of cannabis on fetal development and birth outcomes. We had two objectives: to determine 1) the factors associated with self-reported cannabis use in the pre/early-pregnancy period, and 2) whether cannabis use is associated with low birth weight, preterm birth, or small size for gestational age (GA) infants.MethodsMaternal questionnaire and birth outcome data was gathered from 2229 women and 1778 singleton infants in the Ontario Birth Study, a hospital-based prospective cohort study (2013–2019). Women self-reported cannabis use within 3 months of learning their pregnancy status. Multivariable linear and logistic regression was conducted to 1) identify factors associated with cannabis use, and 2) determine the associations between cannabis use with the selected birth outcomes.ResultsCannabis use increased in the cohort over time. Women who reported cannabis use (N = 216) were more likely to be younger and more likely to use alcohol, tobacco, and prescription pain medication, although most did not. These women had infants born at lower average birth weights and had 2.0 times the odds of being small for GA (95% confidence interval: 1.3, 3.3) after multivariable adjustment for socioeconomic factors and other substance use.ConclusionOur results suggest that women who use cannabis around the time of conception have higher odds of having infants that are small for gestational age. Targeted clinical messaging may be most applicable to women actively trying to conceive.

Fetal safety of chloroquine and hydroxychloroquine use during pregnancy: a nationwide cohort study.

The antimalaria 4-aminoquinoline drugs chloroquine and HCQ are used in the treatment of a wide range of CTDs. Data to inform on the safety of their use in pregnancy are limited. In a Danish nationwide cohort study from 1996 through 2016, we identified 4-aminoquinoline-exposed pregnancies from a cohort of 1 240 875 pregnancies to investigate the associated risks of major birth defects, preterm birth, and small size for gestational age (SGA). Distinct study cohorts of propensity-score-matched 4-aminoquinoline-exposed and unexposed pregnancies (in a 1:1 ratio) were established for each outcome analysis. The association with the outcomes was assessed by prevalence odds ratios (ORs) estimated through logistic regression. The associated risks for chloroquine and HCQ were individually assessed through additional analyses. A total of 1487 pregnancies exposed to 4-aminoquinolines (1184 chloroquine- and 303 HCQ-exposed) were identified. Among the 983 pregnancies exposed to 4-aminoquinolines in the first trimester, 34 infants (3.5%) were diagnosed with major birth defects as compared with 36 (3.7%) among the matched unexposed pregnancies (prevalence OR, 0.94; 95% CI: 0.59, 1.52). Exposure to 4-aminoquinolines in pregnancy was neither associated with an increased risk of preterm birth (prevalence OR, 0.97; 95% CI: 0.73, 1.28) or SGA (prevalence OR, 1.18; 95% CI: 0.93, 1.50), compared with unexposed pregnancies. No significant associations between exposure to chloroquine or HCQ individually and risk of the outcomes were identified. Among pregnancies exposed to 4-aminoquinolines (chloroquine and HCQ), no increased risk of major birth defects, preterm birth, or SGA was identified.

Risk factors during first 1,000 days of life for carotid intima-media thickness in infants, children, and adolescents: A systematic review with meta-analyses.

The first 1,000 days of life, i.e., from conception to age 2 years, could be a critical period for cardiovascular health. Increased carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis. We performed a systematic review with meta-analyses to assess (1) the relationship between exposures or interventions in the first 1,000 days of life and CIMT in infants, children, and adolescents; and (2) the CIMT measurement methods. Systematic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were performed from inception to March 2019. Observational and interventional studies evaluating factors at the individual, familial, or environmental levels, for instance, size at birth, gestational age, breastfeeding, mode of conception, gestational diabetes, or smoking, were included. Quality was evaluated based on study methodological validity (adjusted Newcastle-Ottawa Scale if observational; Cochrane collaboration risk of bias tool if interventional) and CIMT measurement reliability. Estimates from bivariate or partial associations that were least adjusted for sex were used for pooling data across studies, when appropriate, using random-effects meta-analyses. The research protocol was published and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42017075169). Of 6,221 reports screened, 50 full-text articles from 36 studies (34 observational, 2 interventional) totaling 7,977 participants (0 to 18 years at CIMT assessment) were retained. Children born small for gestational age had increased CIMT (16 studies, 2,570 participants, pooled standardized mean difference (SMD): 0.40 (95% confidence interval (CI): 0.15 to 0.64, p: 0.001), I2: 83%). When restricted to studies of higher quality of CIMT measurement, this relationship was stronger (3 studies, 461 participants, pooled SMD: 0.64 (95% CI: 0.09 to 1.19, p: 0.024), I2: 86%). Only 1 study evaluating small size for gestational age was rated as high quality for all methodological domains. Children conceived through assisted reproductive technologies (ART) (3 studies, 323 participants, pooled SMD: 0.78 (95% CI: -0.20 to 1.75, p: 0.120), I2: 94%) or exposed to maternal smoking during pregnancy (3 studies, 909 participants, pooled SMD: 0.12 (95% CI: -0.06 to 0.30, p: 0.205), I2: 0%) had increased CIMT, but the imprecision around the estimates was high. None of the studies evaluating these 2 factors was rated as high quality for all methodological domains. Two studies evaluating the effect of nutritional interventions starting at birth did not show an effect on CIMT. Only 12 (33%) studies were at higher quality across all domains of CIMT reliability. The degree of confidence in results is limited by the low number of high-quality studies, the relatively small sample sizes, and the high between-study heterogeneity. In our meta-analyses, we found several risk factors in the first 1,000 days of life that may be associated with increased CIMT during childhood. Small size for gestational age had the most consistent relationship with increased CIMT. The associations with conception through ART or with smoking during pregnancy were not statistically significant, with a high imprecision around the estimates. Due to the large uncertainty in effect sizes and the limited quality of CIMT measurements, further high-quality studies are needed to justify intervention for primordial prevention of cardiovascular disease (CVD).

A phenome-wide association study of 26 mendelian genes reveals phenotypic expressivity of common and rare variants within the general population

The clinical evaluation of a genetic syndrome relies upon recognition of a characteristic pattern of signs or symptoms to guide targeted genetic testing for confirmation of the diagnosis. However, individuals displaying a single phenotype of a complex syndrome may not meet criteria for clinical diagnosis or genetic testing. Here, we present a phenome-wide association study (PheWAS) approach to systematically explore the phenotypic expressivity of common and rare alleles in genes associated with four well-described syndromic diseases (Alagille (AS), Marfan (MS), DiGeorge (DS), and Noonan (NS) syndromes) in the general population. Using human phenotype ontology (HPO) terms, we systematically mapped 60 phenotypes related to AS, MS, DS and NS in 337,198 unrelated white British from the UK Biobank (UKBB) based on their hospital admission records, self-administrated questionnaires, and physiological measurements. We performed logistic regression adjusting for age, sex, and the first 5 genetic principal components, for each phenotype and each variant in the target genes (JAG1, NOTCH2 FBN1, PTPN1 and RAS-opathy genes, and genes in the 22q11.2 locus) and performed a gene burden test. Overall, we observed multiple phenotype-genotype correlations, such as the association between variation in JAG1, FBN1, PTPN11 and SOS2 with diastolic and systolic blood pressure; and pleiotropy among multiple variants in syndromic genes. For example, rs11066309 in PTPN11 was significantly associated with a lower body mass index, an increased risk of hypothyroidism and a smaller size for gestational age, all in concordance with NS-related phenotypes. Similarly, rs589668 in FBN1 was associated with an increase in body height and blood pressure, and a reduced body fat percentage as observed in Marfan syndrome. Our findings suggest that the spectrum of associations of common and rare variants in genes involved in syndromic diseases can be extended to individual phenotypes within the general population.

Finnish Type Congenital Nephrotic Syndrome With Exon Sequencing Confirmation in Taiwan: A Case Report

Congenital nephrotic syndrome Finnish type (CNF) is a rare and severe kidney disorder starting soon after birth, characterized by premature birth, a small size for gestational age, and an enlarged placenta. Early-onset nephrosis with heavy proteinuria, hyperlipidemia, hypercoagulopathy, and an immunocompromised status often causes poor growth and early mortality if not treated promptly. The current treatment strategy of parenteral albumin supplementation, a hyper-caloric and protein-abundant diet, and medications to prevent and treat complications has improved patient outcomes by making curative renal transplantation possible. This report describes a female newborn diagnosed with CNF incidentally before the onset of symptoms. To the best of our knowledge, she was the first CNF case with a diagnosis confirmed by genetic testing (whole-exon sequencing) in Taiwan.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Association Between Fexofenadine Use During Pregnancy and Fetal Outcomes

Fexofenadine hydrochloride is a frequently used drug for treatment of allergic conditions during pregnancy, but the fetal safety of fexofenadine use has not been well studied. To investigate the risk of adverse fetal outcomes associated with fexofenadine use during pregnancy. A nationwide registry-based cohort study was conducted on pregnancies in Denmark from January 1, 2001, to December 31, 2016. Data analysis was performed from March 21, 2019, to January 29, 2020. From a cohort of 1 287 668 pregnancies, fexofenadine use was compared with cetirizine hydrochloride use during pregnancy, matched in a 1:1 ratio on propensity scores. Distinct study cohorts and exposure time periods were applied according to each outcome analysis. Sensitivity analyses included comparing pregnancies with vs without fexofenadine exposure during pregnancy but with previous use before pregnancy and with loratadine use during pregnancy as additional comparator groups. Filled prescription for fexofenadine. Major birth defects and spontaneous abortion. Secondary outcomes were preterm birth, small size for gestational age (SGA), and stillbirth. Logistic regression was used to estimate prevalence odds ratios (ORs) of major birth defects, preterm birth, and SGA, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) of spontaneous abortion and stillbirth. For the analyses of major birth defects and spontaneous abortion, a total of 2962 and 4901 pregnancies with fexofenadine use were included, respectively, matched in a 1:1 ratio with pregnancies with cetirizine use. Mean (SD) age of the fexofenadine cohort for analyses of major birth defects was 30.6 (4.8) years and, for analysis of spontaneous abortion, 30.4 (5.5) years. Infants born with major birth defects occurred in 118 pregnancies (4.0%) with fexofenadine use compared with 112 pregnancies (3.8%) with cetirizine use. Spontaneous abortion occurred in 413 pregnancies (8.4%) with fexofenadine use compared with 439 pregnancies (9.0%) with cetirizine use. Fexofenadine use during pregnancy was not associated with an increased risk of major birth defects (prevalence OR, 1.06; 95% CI, 0.81-1.37) or spontaneous abortion (HR, 0.93; 95% CI, 0.82-1.07) compared with cetirizine use during pregnancy. Preterm birth occurred in 370 pregnancies (7.5%) with fexofenadine use compared with 382 pregnancies (7.7%) with cetirizine use (prevalence OR, 0.97; 95% CI, 0.83-1.12), SGA occurred in 515 pregnancies (10.1%) with fexofenadine use compared with 523 pregnancies (10.2%) with cetirizine use (prevalence OR, 0.98; 95% CI, 0.87-1.12), and a total of 16 pregnancies (0.3%) with fexofenadine use ended in stillbirth compared with 24 pregnancies (0.4%) with cetirizine use (HR, 0.67; 95% CI, 0.36-1.27). Sensitivity analyses of the primary outcomes, including the comparisons of pregnancies with loratadine use and pregnancies unexposed to fexofenadine during pregnancy but with prior use of fexofenadine, showed similar results. Use of fexofenadine during pregnancy does not appear to be associated with an increased risk of adverse fetal outcomes.

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BackgroundPreterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimester ultrasound in addition to maternal characteristics at the start of pregnancy are optimal to detect fetuses at risk for preterm birth, SGA and LGA.MethodsIn a prospective population-based cohort among 7677 pregnant women, we measured second and third trimester estimated fetal weight (EFW), and uterine artery pulsatility and umbilical artery resistance indices as placenta flow measures. Screen positive was considered as EFW or placenta flow measure < 10th or > 90th percentile. Information about maternal age, body mass index, ethnicity, parity, smoking, fetal sex and birth outcomes was available from questionnaires and medical records. Screening performance was assessed via receiver operating characteristic (ROC) curves and area under the curve (AUC) along with sensitivity at different false-positive rates.ResultsMaternal characteristics only and in combination with second trimester EFW had a moderate performance for screening for each adverse birth outcome. Screening performance improved by adding third trimester EFW to the maternal characteristics (AUCs for preterm birth 0.64 (95%CI 0.61 to 0.67); SGA 0.79 (95%CI 0.78 to 0.81); LGA 0.76 (95%CI 0.75; 0.78)). Adding third trimester placenta measures to this model improved only screening for risk of preterm birth (AUC 0.72 (95%CI 0.66 to 0.77) with sensitivity 37% at specificity 90%) and SGA (AUC 0.83 (95%CI 0.81 to 0.86) with sensitivity 55% at specificity 90%). Combining second and third trimester fetal and placental ultrasound did not lead to a better performance as compared to using only third trimester results.ConclusionsCombining single third trimester fetal and placental ultrasound results with maternal characteristics has the best screening performance for risks of preterm birth, SGA and LGA. As compared to second trimester screening, third trimester screening may double the detection of fetuses at risk of common adverse birth outcomes.

Desloratadine Use During Pregnancy and Risk of Adverse Fetal Outcomes: A Nationwide Cohort Study

Desloratadine is a frequently used drug for the treatment of allergic disorders, which often also require treatment during pregnancy. However, information on the fetal safety of desloratadine use during pregnancy is limited. To investigate the association between desloratadine use during pregnancy and adverse fetal outcomes. From a cohort of 1,287,668 pregnancies identified in the Danish nationwide registries in the study period 2001 to 2016, users of desloratadine and loratadine during pregnancy were matched in a 1:1 ratio based on propensity scores to compare the risk of adverse fetal outcomes. We compared the risk of the primary outcomes major birth defects (among a total of 3348 pregnancies) and spontaneous abortion (5498 pregnancies) and the secondary outcomes preterm birth (5280 pregnancies), small size for gestational age (SGA) for birth weight (5436 pregnancies), and stillbirth (6776 pregnancies). Logistic regression was used to estimate the prevalence odds ratio (OR) of major birth defects, preterm birth, and SGA, and Cox regression to estimate the hazard ratio (HR) of spontaneous abortion and stillbirth. Sensitivity analyses included comparing with cetirizine use in pregnancy and with pregnancies unexposed to desloratadine but with prior use as additional comparator groups. Use of desloratadine in pregnancy was not associated with a significant increased risk of major birth defects (prevalence OR, 1.07; 95% confidence interval [CI], 0.77-1.50), spontaneous abortion (HR, 1.15; 95% CI, 0.96-1.37), preterm birth (prevalence OR, 0.84; 95% CI, 0.67-1.05), SGA (prevalence OR, 0.97; 95% CI, 0.80-1.16), or stillbirth (HR, 0.91; 95% CI, 0.31-2.70) compared with loratadine use in pregnancy. Sensitivity analyses, including those with the use of additional comparator groups, showed similar results. Use of desloratadine during pregnancy was not associated with a statistically significant increased risk of adverse fetal outcomes as compared with loratadine. Results indicate that the fetal safety profile of desloratadine is similar to the currently recommended second-generation antihistamines during pregnancy.

Impact of the Length of Interpregnancy Interval on Obstetric Outcomes

Abstract Background Inter-pregnancy interval (IPI) is defined as the period between the last delivery and conception of the current pregnancy. Both short and long intervals between pregnancies have been associated with an increased risk of variable adverse outcomes, such as preterm birth, low birth weight (LBW), small size for gestational age, and perinatal death. Aim of the Work To assess the impact of IPI as a risk factor for adverse pregnancy and perinatal outcomes. Patients and Methods This study was held in Ain Shams University Maternity Hospital on 1719 patients ranging between the ages of 18-35 years. They were divided into three groups according to the length of their IPI [444 patients in group p1 (6-18 months), 847 patients in group p2 (18-48) and 428 patients in group p3 (&amp;gt; 48 months)]. The aim of this study was to assess the impact of IPI as a risk factor for adverse pregnancy and perinatal outcomes. Results The incidence of LBW among patients with IPI 6-18 months was 11.5%, 12.5% among those with IPI 18-48 months and 16.8% among those with IPI &amp;gt; 48 months. It was also found that the rate of short IPI decreases with age, being more common among the younger age, lower parity groups. The incidence of gestational DM increased with longer IPI. Parity, previous miscarriages, cesarean sections and preterm labor were all significantly associated with the length of IPI. Conclusion This study confirms that both shorter and longer IPIs are associated with increased risks of adverse pregnancy outcomes. This study provides critical information relevant for improving pregnancy outcomes and fetal survival.

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups.

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case–control experimental designs and the study of interactions between different factors it should be emphasized.

Iron Nutrition, Erythrocytes, and Erythropoietin in the NICU: Erythropoietic and Neuroprotective Effects.

Prematurity, maternal diabetes, maternal smoking, being medically underserved, and small size for gestational age are common characteristics of neonates in the NICU and can predispose them to develop congenital iron deficiency. Iron is critical for organ development. In the fetus and newborn, iron is prioritized for red blood cell production, sometimes at the expense of other tissues, including the brain. It is critical to optimize iron levels in newborns to support erythropoiesis, growth, and brain development. Available studies support improved neurodevelopmental outcomes with either iron supplementation or delayed umbilical cord clamping at birth. Erythropoietic doses of erythropoietin/erythrocyte-stimulating agents may also improve neurocognitive outcomes. However, the literature on the effect of liberal red blood cell transfusions on long-term neurodevelopment is mixed. Understanding age-specific normal values and monitoring of iron indices can help individualize and optimize the iron status of patients in the NICU.

Association Between Fetal Safety Outcomes and Exposure to Local Podophyllotoxin During Pregnancy

Podophyllotoxin is an antimitotic agent primarily used in the local treatment of anogenital warts. Data that enable the assessment of the fetal safety of podophyllotoxin use during pregnancy are lacking. To investigate the association between local podophyllotoxin exposure during pregnancy and risk of adverse fetal outcomes. This cohort study obtained individual-level pregnancy data from various nationwide registries in Denmark from the study period of January 1, 1997, through December 31, 2016, resulting in a cohort of 1 650 649 pregnancies. Pregnancies with multiple records on overlapping dates and pregnancy records with implausible or missing information on gestational age were excluded. Local podophyllotoxin-exposed pregnancies were compared with unexposed pregnancies and matched in a 1:10 ratio according to propensity scores on a wide set of baseline characteristics. Five distinct study cohorts were constructed, one for each outcome analysis. Sensitivity analyses included a comparison of podophyllotoxin-exposed pregnancies with pregnancies with podophyllotoxin use only before pregnancy onset. Data analyses were performed from April 27, 2019, to June 26, 2019. Filled prescription for local podophyllotoxin. Primary outcomes were major birth defects and spontaneous abortions. Secondary outcomes were preterm births, small-for-gestational-age (SGA) size, and stillbirths. Logistic regression was used to estimate the prevalence odds ratios (ORs) of major birth defects, preterm births, and SGA size, and Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) of spontaneous abortions and stillbirths. This study included 9229 pregnancies (mean [SD] maternal age at pregnancy onset, 27.7 [5.2] years) for the analyses of major birth defects and 18 590 pregnancies (mean [SD] maternal age at pregnancy onset, 26.4 [6.0] years) for the analyses of spontaneous abortions. Among the podophyllotoxin-exposed pregnancies, 29 infants (3.5%) were diagnosed with major birth defects, compared with 286 (3.4%) among the unexposed pregnancies. A total of 141 podophyllotoxin-exposed pregnancies (8.3%) ended in spontaneous abortion, compared with 1626 (9.6%) among the unexposed pregnancies. No statistically significant associations were found between podophyllotoxin exposure during pregnancy and major birth defects (prevalence odds ratio [OR], 1.02 95% CI, 0.69-1.50), spontaneous abortions (HR, 0.87; 95% CI, 0.73-1.04), preterm births (prevalence OR, 1.08; 95% CI, 0.86-1.35), SGA size (prevalence OR, 1.01; 95% CI, 0.85-1.22), or stillbirths (HR, 0.58; 95% CI, 0.18-1.86). Sensitivity analyses of the primary outcomes achieved similar results. Findings from this study suggest that podophyllotoxin use during pregnancy may be safe, as it did not appear to be associated with an increased risk of adverse fetal outcomes. These findings may help guide clinicians, patients, and drug regulatory authorities when prescribing podophyllotoxin.

Customized versus population birth weight charts for identification of newborns at risk of long-term adverse cardio-metabolic and respiratory outcomes: a population-based prospective cohort study

BackgroundCustomized birth weight charts take into account physiological maternal characteristics that are known to influence fetal growth to differentiate between physiological and pathological abnormal size at birth. It is unknown whether customized birth weight charts better identify newborns at risk of long-term adverse outcomes than population birth weight charts. We aimed to examine whether birth weight classification according to customized charts is superior to population charts at identification of newborns at risk of adverse cardio-metabolic and respiratory health outcomes.MethodsIn a population-based prospective cohort study among 6052 pregnant women and their children, we measured infant catch-up growth, overweight, high blood pressure, hyperlipidemia, liver steatosis, clustering of cardio-metabolic risk factors, and asthma at age 10. Small size and large size for gestational age at birth was defined as birth weight in the lowest or highest decile, respectively, of population or customized charts. Association with birth weight classification was assessed using logistic regression models.ResultsOf the total of 605 newborns classified as small size for gestational age by population charts, 150 (24.8%) were reclassified as appropriate size for gestational age by customized charts, whereas of the total of 605 newborns classified as large size for gestational age by population charts, 129 (21.3%) cases were reclassified as appropriate size for gestational age by customized charts. Compared to newborns born appropriate size for gestational age, newborns born small size for gestational age according to customized charts had increased risks of infant catch-up growth (odds ratio (OR) 5.15 (95% confidence interval (CI) 4.22 to 6.29)), high blood pressure (OR 2.05 (95% CI 1.55 to 2.72)), and clustering of cardio-metabolic risk factors at 10 years (OR 1.66 (95% CI 1.18 to 2.34)). No associations were observed for overweight, hyperlipidemia, liver steatosis, or asthma. Newborns born large-size for gestational age according to customized charts had higher risk of catch-down-growth only (OR 3.84 (95% CI 3.22 to 4.59)). The direction and strength of the observed associations were largely similar when we used classification according to population charts.ConclusionsSmall-size-for-gestational-age newborns seem to be at risk of long-term adverse cardio-metabolic health outcomes, irrespective of the use of customized or population birth weight charts.